Decline in serotonergic firing activity and desensitization of 5-HT1A autoreceptors after chronic unpredictable stress

Eur Neuropsychopharmacol. 2009 Mar;19(3):215-28. doi: 10.1016/j.euroneuro.2008.11.005. Epub 2009 Jan 15.


Chronic stressful life events are risk factors for contracting depression, the pathophysiology of which is strongly associated with impairments in serotonergic (5-HT) neurotransmission. Indeed, in rodents, exposure to chronic unpredictable stress (CUS) produces depressive-like behaviours such as behavioural despair and anhedonia. To date, there have not been many studies that especially explore in vivo changes in 5-HT neurotransmission associated with CUS in the rat. Therefore, using in vivo electrophysiology, we evaluated whether CUS that induces anhedonia-like behaviours concurrently impairs midbrain raphe 5-HT neuronal activity. Unlike unstressed and acutely stressed rats, CUS produced progressive reductions in sucrose intake and preference (anhedonia-like). These were associated with a decrease in the spontaneous firing activity (35.4%) as well as in the number of spontaneously active 5-HT neurons, and a desensitization of somatodendritic 5-HT1A autoreceptors in the dorsal raphe. These results suggest that CUS dramatically decreases 5-HT neural activity and 5-HT1A autoreceptor sensitivity, and may represent endophenotypic features of depressive-like states.

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Analysis of Variance
  • Animals
  • Chronic Disease
  • Disease Models, Animal
  • Drug Interactions
  • Electric Stimulation
  • Food Preferences / drug effects
  • Male
  • Neural Inhibition / drug effects
  • Neurons / drug effects
  • Neurons / physiology*
  • Piperazines / pharmacology
  • Pyridines / pharmacology
  • Raphe Nuclei / pathology
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Serotonin / metabolism*
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin 5-HT1 Receptor Antagonists
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology
  • Stress, Psychological / metabolism*
  • Stress, Psychological / pathology
  • Sucrose / administration & dosage
  • Sweetening Agents / administration & dosage
  • Time Factors


  • Piperazines
  • Pyridines
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin 5-HT1 Receptor Antagonists
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Sweetening Agents
  • Receptor, Serotonin, 5-HT1A
  • Serotonin
  • Sucrose
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
  • 8-Hydroxy-2-(di-n-propylamino)tetralin